William Lee Hearn

Nitrosamine Formation in Bladder Infections and its Role in the Etiology of Bladder Cancer

Dimethylnitrosamine, a powerful carcinogen, is produced in the urine of patients with urinary tract infections of Proteus mirabilis and Escherichia coli when nitrite is present. Treatment with tetracycline antibiotics does not enhance the concentration of this carcinogen but, rather, sharply reduces it. The results emphasize the importance of proper antibiotic therapy for the infections to reduce the possibility of the subsequent development of bladder cancer.

N-Glucuronidation of N-hydroxy aromatic amines: a mechanism for their transport and bladder-specific carcinogenicity.

Abstract Glucuronide conjugates of carcinogenic N -hydroxy metabolites of the primary aromatic amines, 4-aminobiphenyl (4-ABP), 2-naphthylamine (2-NA), and 1-naphthylamine (1-NA) were isolated from the urine of dogs administered the respective primary amine and from the in vitro incubation of N -hydroxy metabolites with uridine-5′-disphosphoglucuronic acid-fortified dog liver microsomes. The urinary and microsomal conjugates were purified by several sequential chromatographic procedures, including Sephadex G-15, Amberlite XAD-2, and cellulose CF-11 chromatography for microsomal conjugates and Sephadex G-10, DEAE, and Amberlite XAD-2 chromatography for urinary conjugates. The infrared spectra of purified urinary and microsomal conjugates of these three N -hydroxy aromatic amines were identical to spectra of authentic Nue5f8C glucuronides prepared by two different synthetic procedures. The urinary and microsomal conjugates comigrated with synthetic Nue5f8C glucuronides in two solvent systems. These observations in conjunction with previous studies provide evidence that Nue5f8C glucuronidation represents a general metabolic reaction of carcinogenic N -hydroxy aromatic amines which provides the means of transport of these compounds to their site of action in the bladder.

Concentrations of nitrate in normal human urine and the effect of nitrate ingestion

Abstract A method suitable for the analysis of nitrate in human urine was developed. Normal urinary concentrations of nitrate in urine of human volunteers in Dade County, Florida, where the drinking water contains negligible amounts of nitrate, averaged 47.6 ppm of NO 3 − (SD = 17.3). On a vegetable and preserved-meat-free diet, the nitrate concentration was reduced (10 to 30 ppm of NO 3 − ), but, on nitrate-supplemented drinking water, the urinary concentration rose to a range of 34–87 ppm of NO 3 − . A high vegetable diet resulted in peak urinary nitrate concentrations of 270–425 ppm. These results indicated that nitrate in drinking water is a factor in determining urinary nitrate concentration, but that vegetable ingestion is of greater significance.

Tissue distribution of cocaine in a pregnant woman

Reports of cocaine-related obstetrical problems, including abruptio placentae and spontaneous abortion, have become increasingly evident in the medical literature; however, little is known about tissue distribution of cocaine in the pregnant woman. We report the toxicologic results of distribution studies performed on a pregnant woman and her fetus. Maternal/fetal cocaine concentration ratios were high when comparing blood (9:1), brain (6:5), and kidney (10:6). Possible explanations of the mechanism for lower fetal cocaine concentrations may include uterine vasoconstriction, incomplete maternal/fetal equalibration, or rapid placental/fetal clearance.

Xylazine Toxicity—Literature Review and Report of Two Cases

Xylazine is a veterinary sedative, analgesic or general anesthetic. Its pharmaceutical action results in sympathetic discharge via stimulation of alpha-2-adrenoceptors. In humans, toxicity consists of central nervous system depression, bradycardia and hypotension. The dosages known to produce toxicity in humans vary from 40 mg up to 2400 mg. Because of decomposition, xylazine blood concentrations in two homicide victims were unknown; however, the concentrations in the brain, liver, and kidneys were much higher in the 23-year-old female versus the 33-year-old male victim. A bottle of xylazine found on the crime scene had a concentration of 100 mg/mL. This 50 mL bottle had 32 mL remaining. Therefore at some point in time 18 mL had been utilized. The amount of available milligrams of xylazine (1800 mg) were enough to cause toxicity in both the woman and the man. Of interest was the fact that the partially skeletonized heads were found remote from the torsos, however, the concentration of xylazine in the body tissues provided a toxicological match of which head belonged to which body. Xylazine toxicity in humans and its relationship to these homicides will be the focus of this report.

Death from Pool Chlorine—An Unusual Case

A tank truck containing bulk pool chlorinating solution overturned. A man was trapped beneath the truck, and a ruptured seam in the tank released a continuous flow of sodium hypochlorite over him. He survived for 10 min as the caustic solution extensively eroded soft tissue exposed to the chemical flow.

Drug Contamination of U.S. Paper Currency and Forensic Relevance of Canine Alert to Paper Currency: A Critical Review of the Scientific Literature

Several studies have reported on wide‐spread contamination of U.S. paper currency with cocaine and to a lesser extent other illicit drugs. Canines are trained and employed to search for and alert to drugs. Canine alert to currency has been used as evidence that currency has been directly involved in illicit drug trafficking to justify currency seizure and forfeiture. This assertion, particularly when the only evidence is based upon canine alert, has been challenged in the courts considering that most currency in circulation is contaminated with cocaine. Comprehensive review of the scientific literature establishes that (i) 67–100% of circulated U.S. currency is contaminated with cocaine ranging from a few nanograms to over one milligram/bill (ii) various biological and environmental parameters impact canine alert to drugs. It is concluded that canine alert to U.S. currency is not sufficiently reliable to determine that currency was directly used in an illicit drug transaction.

Development of sarcomas in heterotopically transplanted rat urinary bladder unit exposed to glucuronic acid conjugate of N-hydroxy-4-aminobiphenyl

The glucuronic acid conjugate of N-hydroxy-4-aminobiphenyl was tested for carcinogenicity using a heterotopically transplanted rat urinary bladder (HTB) diverted from urine flow. A low-grade transitional cell carcinoma developed in 1 of 16 HTB and sarcoma surrounding the Ommaya reservoir connected to HTB in 8 of 16 rats. This unexpected high incidence of sarcomas, not previously observed in HTB-carcinogenesis model, suggested that the glucuronide conjugate of N-hydroxy-4-aminobiphenyl is a locally active carcinogen to mesenchymal cells.